Methanol → HCID 15453176, compound

HRID 1167011Notes

Reaction equation

HRID 1167011 reaction equation
[H-].[Na+].[NH2:3][C:4]1[O:8][N:7]=[C:6]([CH3:9])[C:5]=1[Cl:10].[C:11]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:16]=[CH:15][C:14]([S:17](Cl)(=[O:19])=[O:18])=[CH:13][CH:12]=1.CO>C1COCC1.O>[Cl:10][C:5]1[C:6]([CH3:9])=[N:7][O:8][C:4]=1[NH:3][S:17]([C:14]1[CH:13]=[CH:12][C:11]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:16][CH:15]=1)(=[O:19])=[O:18]

Participants

7

Reactant 4

HCID 887MethanolHCID 24758Sodium hydride2×HCID 74192(1,1'-Biphenyl)-4-sulphonyl chlorideHCID 105828224-Chloro-3-methyl-1,2-oxazol-5-amine

Product 1

HCID 15453176HCID 15453176, compoundYield 83%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Sodium hydride (188 mg, 4.4 mmol) was suspended in dry THF (1 ml) and cooled to 0° C. A solution of 5-amino-4-chloro-3-methylisoxazole (mg, mmol) in dry THF (1 ml) was added with stirring. Once the addition was complete, the reaction mixture was warmed to room temperature for 10 min. The solution was recooled to 0° C., and 4-biphenylsulfonyl chloride (0.283 ml, 2.2 mmol) was added. Stirring was continued at 25° C. for 2 h. Excess sodium hydride was decomposed by the addition of methanol (0.4 ml) followed by water (0.5 ml). The THF was removed under reduced pressure and the residue was dissolved in water (20 ml) and basified by addition of sodium hydroxide (pH 9-10). Neutral impurities were removed by extraction with ethyl acetate (2×10 ml). The aqueous layer was acidified to pH 2-3 using concentrated HCl and extracted with ethyl acetate (3×10 ml). The combined organic layer was dried over magnesium sulfate. Removal of the solvent gave N-(4-chloro-3-methyl-5-isoxazolyl)-4-biphenylsulfonamide in 83% yield. This product was purified by recrystallization from ethyl acetate/hexanes as a white solid, m.p. 129-132° C.

Workup

  1. additionOnce the addition
  2. temperaturethe reaction mixture was warmed to room temperature for 10 min
  3. customwas recooled to 0° C.
  4. stirringStirring
  5. customThe THF was removed under reduced pressure
  6. dissolutionthe residue was dissolved in water (20 ml)
  7. additionbasified by addition of sodium hydroxide (pH 9-10)
  8. customNeutral impurities were removed by extraction with ethyl acetate (2×10 ml)
  9. extractionextracted with ethyl acetate (3×10 ml)
  10. dry with materialThe combined organic layer was dried over magnesium sulfate
  11. customRemoval of the solvent

Sources & evidence

ORD record
ord-10ddd01d7ab54750a1c29e30dd0ce118
Source dataset
uspto-grants-2003_09
Patent number
US06613804B2

Reaction notes

Loading…